Talk:HIV-1 protease

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Catalytic mechanism

It cleaves the envelope polyprotein gp160 into envelope glycoproteins gp120 and gp41 in the golgi apparatus in the final stages of the HIV life-cycle.

apparently this line was incorrect. I don't really know, but if anyone out there knows can they please describe the exact reaction catalyzed by this protease? Roadnottaken 21:53, 1 September 2007 (UTC)

gp160 does get cleaved into gp120 + gp41. That line is probably incorrect in the sub-cellular localization of this reaction to the Golgi. I'm not sure exactly where this happens, though. Its in the field lit. —Preceding unsigned comment added by Argantael (talk • contribs) 17:28, 21 April 2009 (UTC)

HIV-1 protease topology

The article currently mentions only the naming proposed by Perryman. The image caption in his original paper mentions another nomenclature as a "convention" (implying that it is more widespread) so this seems like undue weight to me. I've tried to find some source describing the "convention", but have not come up with anything yet. Does anyone know perhaps of any paper discussing it? --Eleassar ^{my talk} 12:27, 1 July 2008 (UTC)

Sorry for not responding sooner. I have been looking for HIV-1 protease naming conventions and so far I have not found any beyond the most basic "flap" and "hinge" terminology. I am still looking. Cheers. Boghog2 (talk) 13:39, 2 July 2008 (UTC)

Does anyone object to removal of the inbalanced/inaccurate flag on this section? In my research I have not come across anything other than Perryman's system and "flap"/"hinge" naming. Other researchers are using Perryman's system. The flag is a bit obtrusive, and I don't know that it's necessary. Biscotta (talk) 17:26, 24 February 2009 (UTC)

Hehe, I think the flap is obtrusive too. I guess its okay to represent in this article the plain fact that this is SOME of the terminology used when referring to structure-function details of this molecule, but the dog and cat comparisons are colloquial aids in structure-function annotation. The actual molecular regions indicated by the names may be functionally distinct, but they might be a sort of "paraphyletic" comparison, divergent from the real structure-function sub-domains or regions of the molecule. That's how you would address this naming issue. Argantael (talk) 17:32, 21 April 2009 (UTC)

References

Linking to Proteopedia

I added an external link, one to a page in another wiki resource called Proteopedia. The page I linked to provides a 3d interactive structure of HIV-1 protease with hyperlinks in the text (appearing as clickable green links), that when clicked, prompt changes in the 3d structure to reflect concepts described in the text. This link was removed and the user that removed it cited that the link was in violation of WP: ELNO 1 and 12. This is not the case. Linking to Proteopedia articles does not violate WP ELNO 1 because even if the Wikipedia article were a full featured article, it would not contain interactive 3d visualizations of the protein structure. It also does not violate WP ELNO 12 because Proteopedia is not an open wiki. Only registered users may edit pages in Proteopedia, and only members of the scientific community are invited to request accounts. —Preceding unsigned comment added by 132.77.4.129 (talk) 16:50, 20 August 2008 (UTC)

HIV-1 protease as a drug target

I'd like to add information on drugs that target this enzyme. For now, perhaps just the FDA-approved ones (Saquinavir, Indinavir, Nelfinavir, Fosamprenavir, Atazanavir, Tipranavir, Darunavir, Lopinavir), because I don't know if I'm up for cataloging every HIV protease inhibitor in clinical trials. But I think this section should focus more on HIV protease. Any objections? (I'm new at this, sorry if I mess up formatting or any such thing.) Biscotta (talk) 17:27, 24 February 2009 (UTC)

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Rough Outline

I would like to restructure this page {and add additional sections} and the following information:

• {Synthesis}
  • HIV-1 Protease is originally a part of the Gag-Pol polyprotein precursor but undergoes autoprocessing, an enzymatic activity for production of the same enzyme, via its precursor domain that ultimately cleaves mature HIV-1 protease proteins for cleaving other mature viral proteins from the polyprotein.
    • ## I just thought that this part of the current version of the article ("HIV protease is encoded within the pol gene, and is cleaved out by HIV protease") was a bit ambiguous.
  • Draft: The precursor domain of HIV-1 protease, encoded within the pol gene and a component of the Gag-Pol polyprotein, catalyzes its own production by facilitating the cleavage of functional HIV-1 proteases, a mechanism known as autoprocessing.
    • Mechanism for synthesis:
      • Intramolecular cleavage of N-terminus, followed by intermolecular cleavage of C-terminus
      • Evidence that HIV-1 protease autoprocessing is mediated by folding
• Structure
  • Precursor: 17 kDa with 161 residues
    • Structure: TFR-PR-Cⁿⁿ
      • TFR is the N-terminus transframe region
      • PR is an abbreviation for the HIV-1 protease
      • Cⁿⁿ refers to the 5-residue extension at the C-terminus
  • Mature Protein: 22kDa homodimer with 99 residues on each subunit
• Function
  • HIV-1 protease not only mediates its own release, but its fully functional form cleaves out other proteins essential for viral synthesis.
    • I would like to add brief information of some of the important proteins that it cleaves out
• {Mechanism}
  • A protease is a catalytic protein (specifically, a hydrolase) that cleaves polypeptides with the addition of water.
  • ##I would like to add information about the specific roles of the residues in this protease's catalytic triad (Asp-Thr-Gly)
    • Aspartate of triad involved in catalysis
    • Dimerization of the two protease subunits allows for the active site containing these catalytic triads to form
• HIV-1 Protease as a Drug Target
  • ##I would like to add a more detailed description of the chemical mechanism regarding how the inhibitors bind to the active site of HIV-1 protease
  • ##I would like to add more information about the functionally critical regions of the HIV-1 protease that render this area a target for enzyme inhibition
• {Evolution}
  • ##I would like to include more information about increasing HIV-1 protease resistance to inhibitors due to recombinants with different structural configurations from the wild type

1. Please let me know if you have any suggestions! Thanks! — Preceding unsigned comment added by MBae2 (talk • contribs) 21:35, 10 May 2018 (UTC)

References

Questions

• What is HIV protease? In the lead section, The term, "HIV protease" is suddenly used, without having been properly introduced. Is it a misprint of "HIV-1 protease"? Polar Apposite (talk) 17:08, 11 January 2024 (UTC)

Both HIV-1 and HIV-2 have a similar protease enzyme. HIV-1 PR and HIV PR appear to be used interchangeably in at least some of the sources. No changes needed that I can see to the generic term, though some discussion of the protein's role and any differences in HIV-2 would be a nice add if there is sourcing. VQuakr (talk) 18:49, 11 January 2024 (UTC)

I don't think I know enough about biology to do that. In the mean time wouldn't it be best to change "HIV PR" to "HIV-1 PR"? At the very least, it would make the article easier to read for the layman. Please try to imagine the perspective of the layman. He or she will have *no* idea why the one is suddenly missing. Polar Apposite (talk) 19:52, 12 January 2024 (UTC)

HIV and its variants are already wikilinked and pretty common knowledge to anyone vaguely familiar with the general topic. They are obviously related terms so I think the risk of confusion is nil, but the source does appear to consistently spell out HIV-1 so I can change it shortly. VQuakr (talk) 00:35, 13 January 2024 (UTC)

The survey article [1] does note some drug efficacy differences between HIV-1 and HIV-2. More digging needed. VQuakr (talk) 00:58, 13 January 2024 (UTC)

ETA#2 - HIV-2 protease is its own article. VQuakr (talk) 01:25, 13 January 2024 (UTC)

• What is essential? "It is an enzyme involved with peptide bond hydrolysis in retroviruses that is essential for the life-cycle of HIV, which is the retrovirus that causes AIDS." Is it the enzyme that is essential, or the hydrolysis that is essential, (or both)? Once I know, I will be in a better position to clarify the meaning, perhaps by adding some commas. Polar Apposite (talk) 17:11, 11 January 2024 (UTC)

Both the protein and the hydrolysis it performs are essential to the virus's pathogenicity. I think the sentence is already clear. VQuakr (talk) 18:49, 11 January 2024 (UTC)

There is something called the curse of knowledge, where one's extremely deep knowledge of, and familiarity with, a topic makes it difficult to explain it properly to a layman, or even an undergraduate student of the subject. The curse of knowledge can cause an explanation of something to be at kindergarten level (figuratively speaking) and therefore adequate for an intelligent layman, when in reality it is opaque to any and all laymen. Perhaps because I hadn't even heard of this enzyme before stumbling on this article, I can see that the sentence is unclear. Polar Apposite (talk) 20:14, 12 January 2024 (UTC)

Our articles are not written at the kindergarten level, figuratively or otherwise. In particular, top-level articles can be expected to be more introductory than more detailed ones. In this case, the drilldown is Biology -> Biochemistry -> Protein -> Enzyme -> Protease -> HIV-1 protease. Pretty deep in the weeds, and our audience isn't expected to be a reader with no background in the general topic. VQuakr (talk) 00:35, 13 January 2024 (UTC)

• "The Gag-Pol polyprotein, which contains premature coding proteins, including HIV-1 PR. PR is located between the reverse transcriptase (which is at the C-terminus of PR) and the p6^pol (which is at the N-terminus of PR) of the transframe region (TFR)." What is "PR"? Does "PR" mean "HIV-1 PR"? If so, it should be introduced properly as an abbreviation prior or at its first use in the article. Polar Apposite (talk) 17:18, 11 January 2024 (UTC)

As defined parenthetically in the first sentence of the lead, PR is an abbreviation of protease. No changes needed here. VQuakr (talk) 18:49, 11 January 2024 (UTC)

It may be normal to write like that in journal articles on this topic, but the lead section (the whole article?) is supposed to be layman-friendly. The first sentence of the lead section starts, "HIV-1 protease (PR)" while the title of the article is "HIV-1 protease". This may be fine for experts, but the layman will not know what "PR" means. It could be that "PR" means "HIV=1 protease", or that "PR" means "protease", or it could be that the (PR) is part of the name, not an abbreviation for it. The layman will have no clue which of these interpretations is the right one. It is terrible writing, if intended to be read by the layman. Polar Apposite (talk) 20:02, 12 January 2024 (UTC)

How about [2]? VQuakr (talk) 00:35, 13 January 2024 (UTC)